8gs8

cryo-EM structure of the human respiratory complex IIcryo-EM structure of the human respiratory complex II

Structural highlights

8gs8 is a 4 chain structure with sequence from Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:	Electron Microscopy, Resolution 2.86Å
Ligands:	, , , , , ,
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

SDHA_HUMAN Familial isolated dilated cardiomyopathy;Hereditary pheochromocytoma-paraganglioma;Gastrointestinal stromal tumor;Isolated succinate-CoQ reductase deficiency. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry. The disease is caused by variants affecting the gene represented in this entry.

Function

SDHA_HUMAN Flavoprotein (FP) subunit of succinate dehydrogenase (SDH) that is involved in complex II of the mitochondrial electron transport chain and is responsible for transferring electrons from succinate to ubiquinone (coenzyme Q) (PubMed:24781757). Can act as a tumor suppressor (PubMed:20484225).^[1] ^[2]

Publication Abstract from PubMed

Human complex II is a key protein complex that links two essential energy-producing processes: the tricarboxylic acid cycle and oxidative phosphorylation. Deficiencies due to mutagenesis have been shown to cause mitochondrial disease and some types of cancers. However, the structure of this complex is yet to be resolved, hindering a comprehensive understanding of the functional aspects of this molecular machine. Here, we have determined the structure of human complex II in the presence of ubiquinone at 2.86 A resolution by cryoelectron microscopy, showing it comprises two water-soluble subunits, SDHA and SDHB, and two membrane-spanning subunits, SDHC and SDHD. This structure allows us to propose a route for electron transfer. In addition, clinically relevant mutations are mapped onto the structure. This mapping provides a molecular understanding to explain why these variants have the potential to produce disease.

Structure of the human respiratory complex II.,Du Z, Zhou X, Lai Y, Xu J, Zhang Y, Zhou S, Feng Z, Yu L, Tang Y, Wang W, Yu L, Tian C, Ran T, Chen H, Guddat LW, Liu F, Gao Y, Rao Z, Gong H Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2216713120. doi: , 10.1073/pnas.2216713120. Epub 2023 Apr 25. PMID:37098072^[3]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Burnichon N, Brière JJ, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E, Jeunemaitre X, Bénit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1;19(15):3011-20. PMID:20484225 doi:10.1093/hmg/ddq206
↑ Renkema GH, Wortmann SB, Smeets RJ, Venselaar H, Antoine M, Visser G, Ben-Omran T, van den Heuvel LP, Timmers HJ, Smeitink JA, Rodenburg RJ. SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Eur J Hum Genet. 2015 Feb;23(2):202-9. PMID:24781757 doi:10.1038/ejhg.2014.80
↑ Du Z, Zhou X, Lai Y, Xu J, Zhang Y, Zhou S, Feng Z, Yu L, Tang Y, Wang W, Yu L, Tian C, Ran T, Chen H, Guddat LW, Liu F, Gao Y, Rao Z, Gong H. Structure of the human respiratory complex II. Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2216713120. PMID:37098072 doi:10.1073/pnas.2216713120

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OCA

[1] Burnichon N, Brière JJ, Libé R, Vescovo L, Rivière J, Tissier F, Jouanno E, Jeunemaitre X, Bénit P, Tzagoloff A, Rustin P, Bertherat J, Favier J, Gimenez-Roqueplo AP. SDHA is a tumor suppressor gene causing paraganglioma. Hum Mol Genet. 2010 Aug 1;19(15):3011-20. PMID:20484225 doi:10.1093/hmg/ddq206

[2] Renkema GH, Wortmann SB, Smeets RJ, Venselaar H, Antoine M, Visser G, Ben-Omran T, van den Heuvel LP, Timmers HJ, Smeitink JA, Rodenburg RJ. SDHA mutations causing a multisystem mitochondrial disease: novel mutations and genetic overlap with hereditary tumors. Eur J Hum Genet. 2015 Feb;23(2):202-9. PMID:24781757 doi:10.1038/ejhg.2014.80

[3] Du Z, Zhou X, Lai Y, Xu J, Zhang Y, Zhou S, Feng Z, Yu L, Tang Y, Wang W, Yu L, Tian C, Ran T, Chen H, Guddat LW, Liu F, Gao Y, Rao Z, Gong H. Structure of the human respiratory complex II. Proc Natl Acad Sci U S A. 2023 May 2;120(18):e2216713120. PMID:37098072 doi:10.1073/pnas.2216713120

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